Recognition memory can be based on recollection of qualitative information about previous events, or on assessments of stimulus familiarity. These two processes are functionally distinct and are supported by separate sub-regions of the medial temporal lobes. The long-term goal of the proposed studies is to determine the cortical substrates and functional properties of the processes supporting recognition memory, which will provide a foundation for accurate diagnosis and rehabilitation protocols for neurological patients suffering from memory impairments. The specific aims of the current proposal are to: 1) Investigate the role of prefrontal cortex in recollection and familiarity. Although the prefrontal cortex is critical for human memory, we currently do not know how this region contributes to recollection and familiarity. The proposed studies will determine the role of the prefrontal cortex in recollection and familiarity by examining the effects of left and right lateral prefrontal lobe damage on these forms of memory in human neurological patients. The studies will characterize the mnemonic functions of the prefrontal cortex and allow direct tests of competing theories of human recognition memory. 2) Determine if conceptual implicit memory relies on regions in the temporal lobes and prefrontal cortex. It is currently debated whether familiarity reflects a form of implicit memory. Previous studies have demonstrated that familiarity and perceptual implicit memory (e.g., fragment completion) can be functionally dissociated, and that they rely on separate brain regions. It remains unknown, however, if the brain systems supporting familiarity are involved in conceptual implicit memory (e.g., exemplar generation). We will examine conceptual implicit memory in patients with damage to different temporal lobe regions and patients with damage to the lateral prefrontal cortex. The studies will be critical in determining the brain regions necessary for conceptual implicit memory and in resolving the debate about the cognitive-neural mechanisms underlying familiarity and implicit memory. 3) Determine the conditions under which familiarity can support recognition memory for novel associations. A core assumption underlying many current theories of recollection - and of hippocampal function - is that recollection is necessary for associating or binding different aspects of an event together in long-term memory. However, recent evidence indicates that familiarity can support associative learning under certain conditions. Two competing explanations for these results have been proposed: 'within-domain' theories predict that familiarity can support associative recognition only when the association is between items from the same processing domain, whereas 'unitization' theories predict that familiarity will be useful only when the associated items are encoded as a single unit. We will examine the effects of unitization and of changing processing domains on familiarity-based associative memory in healthy controls and in amnesic patients with preserved familiarity judgments (e.g., hypoxic patients) in order to determine the conditions under which familiarity can support associative learning. These studies will be essential in understanding how the brain supports learning of novel associations, and will provide the first direct test of competing theories of familiarity.